key: cord-0003535-6gljrj8r
authors: Duong, Theresa N.; Zeki, Amir A.; Louie, Samuel
title: Medical Management of Hospitalized Patients with Asthma or Chronic Obstructive Pulmonary Disease
date: 2017-10-01
journal: Hospital Medicine Clinics
DOI: 10.1016/j.ehmc.2017.05.002
sha: 0b4d934c724fd26eedb928364971f18175a2f0e3
doc_id: 3535
cord_uid: 6gljrj8r

nan

noxious particles or gases. The small airways in COPD are gradually destroyed leading to chronic bronchitis and emphysema. 1 COPD is typically preventable with removing exposure to the noxious substance. Emphysema is not present in asthma but is a key pathologic feature of COPD. At present, there is no cure for either of these conditions. The goals during hospitalization for asthma and COPD are similar: to prevent acute respiratory failure and complications from hospital management.

The imminent danger during acute exacerbation of asthma or COPD is unrecognized and sustained cerebral hypoxia from acute respiratory failure, primarily from ventilation-perfusion mismatching and hypoventilation. Profound respiratory fatigue and exhaustion from increased work of breathing for days before admission contribute to the acute danger of an exacerbation. In asthma and COPD, the immediate goal is to guard against hypoxia with supplemental oxygen and to relieve dyspnea with short-acting beta-agonist bronchodilators with or without ipratropium bromide. The main goal is to avoid further respiratory compromise and failure. The 30-day mortality from acute COPD exacerbation is between 11% and 26% (more fatal than acute myocardial infarction), and approximately 340 patients with COPD and 10 asthmatics die each day in the United States. [2] [3] [4] The management of both diseases is similar. The fundamental difference from the home setting is close respiratory monitoring by registered nurses and respiratory therapists. In addition, noninvasive ventilation (NIV), particularly for patients with COPD, is available, and prevents the need for invasive mechanical ventilation, and associated risk of pneumonia. In severe stage 4 COPD, direct admission for hospice can be considered. Patients with asthma and COPD are hospitalized when they cannot manage at home, often indicated by the failure to improve with frequent albuterol use over a 2-or 3-day period. In both diseases, antibiotics and intravenous corticosteroids may shorten duration of symptoms and length of hospital stay, and prevent respiratory failure. On hospital discharge, patient with asthma or COPD benefit from outpatient transitional care services and instructions for follow-up care to ensure patient safety and prevent hospital readmission.

Differentiating asthma from COPD in an undiagnosed hospital patient can be difficult. This problem has led to the recognition of asthma-COPD overlap syndrome (ACOS) (discussed later). The diagnosis of asthma or COPD is based primarily on clinical features of each individual case.

A focused and detailed clinical history along with inpatient spirometry near the end of the patient's hospital may assist with the diagnosis of asthma or COPD ( Table 1) . However, severe asthma may be indistinguishable from moderate and severe COPD on spirometry alone. The finding of a low carbon monoxide diffusing capacity suggests pulmonary emphysema and COPD, but these data are often not available. Emphysema on thoracic imaging can assist with the diagnosis of COPD. A low carbon monoxide diffusing capacity in asthmatics should raise suspicion for another diagnosis (eg, asthmatic granulomatosis, bronchiolitis obliterans, and pulmonary arterial hypertension).

Asthma is often diagnosed when forced expiratory volume in 1 second (FEV 1 ) improves after bronchodilator treatment; however, nearly two-thirds of patients with COPD can show the same response. 5 Use of bronchodilator responsiveness is of little clinical value in distinguishing asthma from COPD. Some asthmatics do not show responsiveness until they have had 2 to 3 weeks of corticosteroid treatment. 4 Although smoking is a risk factor for emphysema and COPD, only 20% of chronic smokers develop COPD. 6 The following questions can help differentiate between asthma and COPD, but this needs to be put into the context of the clinician's suspicion, experience, and patient response to treatments. 4, 7 Of note, patients with ACOS may have all the symptoms mentioned here; therefore, consider consulting a pulmonologist. In summary, both patients with asthma and those with COPD respond very well to bronchodilators. Notably, adult asthmatics may never return to baseline if they have a history of a FEV 1 to forced vital capacity ratio (FEV 1 /FVC) that is less than predicted for their age.

Evaluation, management, and postdischarge plan for acute asthma exacerbation Immediate assessment and intervention is the best strategy when evaluating acute asthma exacerbations because they can become life threatening as the patient moves from the emergency department to the hospital ward. Fig. 1 presents the recommended algorithm by the National Asthma Education and Prevention Program -Expert Panel Report (2007) .

Expect patients with uncomplicated asthma to require 4 to 6 days in the hospital. A decrease in need for rescue albuterol use, walking without dyspnea on exertion, and the ability to sleep all night are all signs the patient may be safely discharged.

On discharge, to prevent relapse and rehospitalization, the following steps are recommended:

1. If the patient is not already using an inhaled corticosteroid (ICS), start treatment. 2. One day before discharge, change to the patient's outpatient regimen. Early initiation of home regimen helps with education, ensures adequate medication technique, and initiates therapy to overlap with systemic corticosteroids. 3. Discharge with a short-acting beta-agonist (SABA), flow chamber device, and oral corticosteroid for a course of 5 to 10 days pending clinical assessment. The authors recommend a 12-day taper as follows: prednisone 40 mg PO  3 days, 30 mg PO  3 days, 20 mg  3 days, 10 mg PO  3 days, then stop. We do not Abbreviations: CBC, complete blood count; CXR, chest radiograph; FEV 1 , forced expiratory volume in 1 second; FVC, forced vital capacity; IgE, immunoglobulin E. a This is the strongest identifiable predisposing factor for developing asthma. 7 b ImmunoCAP detects specific IgE antibodies in the blood to rule in or rule out atopy in patents with allergy-like symptoms. c For work-up of COPD, age may play a factor in interpretation of FEV 1 /FVC. An FEV 1 /FVC less than 0.70 may be normal in an older individual (ie, >65 years old).

recommend treatment for more than 2 weeks because adrenal insufficiency can occur. 4. Education on asthma prevention (avoiding triggers, smoking cessation, peak flow meter use) and outpatient follow-up within 2 weeks. 5. For patients with severe asthma, consider adding a long-acting muscarinic antagonist (LAMA) to combination therapy with a long-acting beta agonist (LABA)1ICS, 8 to improve asthma symptom control and lung function. ICS 1 LABA 1 LAMA is considered 'triple therapy', which may offer better symptom control compared with dual ICS 1 LABA therapy. 6. Pulmonary clinic referral is indicated for recurrent asthma exacerbations, hospitalizations, or life-threatening exacerbation. Also, refer for evaluation of further medical optimization or bronchial thermoplasty.

A COPD exacerbation is an acute sustained worsening from baseline functional status, with common symptoms of worsening cough, breathlessness, change in sputum color, and increased sputum production. A COPD exacerbation accelerates natural disease progression by contributing to the permanent loss of lung function. If recovery of an exacerbation is slow then patients are more likely to have disease progression and are at an increased risk of additional COPD exacerbations in the future. Thus, it is imperative for physicians to understand the common causes of exacerbations, and the need for quick assessment of severity and facile medical management of exacerbations before progression respiratory failure.

The most common cause of exacerbations is infectious, primarily viruses and bacteria (Box 1). 9,10 However, noninfectious triggers and other comorbid conditions must be considered.

More than 80% of exacerbations can be managed on an outpatient basis. 1 Health-care providers benefit from being familiar with the classifications of COPD exacerbations:

Mild (treatment with short-acting bronchodilators) Moderate (treatment with SABAs, antibiotics, and/or oral corticosteroids) Severe (requires hospitalization or emergency room visit for acute respiratory failure)

For hospitalized patients, classification of exacerbation severity can help triage the patient to the appropriate level of care ( Table 2 ) 1,11,12 and then consider using the algorithm shown in Fig. 2 to guide decision making.

The overall goal for treatment of a COPD exacerbation focuses on minimizing the negative impact of the current exacerbation and preventing the likelihood of future exacerbations ( Table 3) .

Interdisciplinary inpatient management at UC Davis Medical Center in Sacramento, California, involves the pulmonary and hospitalist divisions. Trained respiratory therapists act as COPD case managers. COPD case managers coordinate care, including medication reconciliation and COPD education; work with discharge planning, social This interdisciplinary program has reduced unplanned 30-day hospital readmissions for all causes to 6.6% from a historical 16% at UC Davis Medical Center. 13 Therefore, patients with COPD can better manage their disease and improve primary prevention and disease outcomes postdischarge.

The postdischarge checklist for COPD exacerbations and the clinical reasoning behind each intervention can be seen in Table 4 .

Patients with ACOS have persistent airflow limitation with overlapping features of asthma and COPD. 14 ACOS accounts for approximately 15% to 55% of patients with chronic airflow limitation. 15 ACOS is associated with a higher risk for exacerbations, and increased frequency and severity of acute exacerbation compared with COPD or asthma alone. [16] [17] [18] [19] ACOS is associated with higher health care use, more progressive lung disease, and lower health care-related quality of life compared with asthma or COPD alone. 16, [18] [19] [20] No evidence-based guidelines distinguishing asthma, COPD, and ACOS are available to date because patients with ACOS have historically been excluded from randomized clinical trials. Therefore, there are no evidence based guidelines that can guide therapy specifically for ACOS. For clinicians, the tool shown in Fig. 3 is a syndromic approach proposed by a collaboration between the Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung (GOLD) in 2015. 

When ACOS is diagnosed in the outpatient setting, the recommendation is to treat for asthma first, 15 which means starting an ICS, which shows how important the control of inflammation is in this disease. However, during acute exacerbations requiring hospitalization, both disease components require treatment.

To date there are no evidence-based guidelines directing ACOS treatment. Therefore, treatment should be based on the available evidence in asthma and COPD, GINA and GOLD organization guidelines, the practitioner's clinical experience, and the patient's clinical response to treatment. A suggested guideline from the authors is given here:

Consider inpatient pulmonary consultation given the greater disease severity and higher morbidity and mortality of patients with ACOS. A comprehensive discharge plan in a patient with suspected ACOS facilitates further outpatient work-up and prevents repeated readmissions: ICS (low or moderate dose) with LABA AE LAMA; avoid LABA monotherapy in ACOS because there is a FDA warning against LABA monotherapy in asthma Rescue SABA Referral to a pulmonary specialist for further diagnostic work-up and management Referral/resources for smoking cessation, counseling on physical activity, referral to pulmonary rehabilitation, and treatment of comorbid conditions

Patients with AECOPD are at increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) and should receive thromboprophylaxis while hospitalized. 1 The prevalence of PE in unexplained AECOPD is estimated at 16%, and two-thirds of emboli are in the proximal pulmonary arteries, which is clinically significant and requires anticoagulation. 21 Evaluate for PE when there is no clear infectious origin, there is pleuritic chest pain, and signs of cardiac-associated disorder (syncope, acute heart failure). 21, 22 Asthmatics, especially severe asthmatics and those with frequent hospitalizations, have a significant risk for developing a PE and/or DVT. 23, 24 At the time of this writing, there are no clear evidence-based or clinical guidelines on when to work up PE in the setting of asthma or AECOPD. The authors recommend using clinical suspicion and pretest probability to stratify patients with suspected PE. Consider using clinical decision tools (e.g., Wells score) before ordering tests to diagnosis PE in this population.

Because both COPD and asthma are risk factors for thromboembolic events, patients with ACOS have also been found to have increased risk of PE. 25 ACOS is an emerging disease entity and further clinical research must be done to further characterize its relationship to venous thromboembolic disease.

Bronchodilators are the first-line therapy and mainstay of treatment used to improve lung function; this is achieved by bronchial smooth muscle relaxation, decreased airway inflammation, reduced air-trapping, and reduced mucous plugging. For symptomatic patients on long-acting monotherapy with a LAMA or LABA, per the GOLD 2017 guidelines, it is recommended to start a combination LAMA 1 LABA because this improves lung function and patient outcomes more effectively. 1, 26 Asthma ICSs are the first-line therapy and the mainstay of treatment for long-term control of asthma because of their antiinflammatory actions.

The US Food and Drug Administration issued a black-box warning for all LABAs because there is an increased risk of death. Nevertheless, LABA currently remains the preferred add-on bronchodilator for those on ICS. 4 Adding a LABA to ICS as combination therapy should be considered in patients 5 years of age or older who are not sufficiently controlled with ICS alone or who need increasing doses of ICSs. 4 LABA monotherapy in asthma is contraindicated. Alternatively, at UC Davis, a LAMA inhaler is added to ICS monotherapy or to ICS 1 LABA combination with similar results to the published literature. 27, 28 Novel Therapies for Chronic Obstructive Pulmonary Disease and Asthma

There are some novel therapies not yet included in the guidelines, because studies examining these agents are too small or are undergoing investigation ( Table 5) . 1, 26, [29] [30] [31] [32] [33] [34] [35] Newer agents are LABAs combined with LAMAs in a pressurized MDI, soft-mist inhaler, or dry-powder inhaler. For hospitalists, familiarity with these newer agents (see Table 5 ) helps optimize medical management on hospital discharge.

Disease control in asthma is essential before any kind of surgery. Well-controlled asthma (per the Asthma Control Test [ACT] is a score of 20 or more) is obviously preferable to very poorly controlled asthma (ACT score 15). Asthmatics are at risk for several complications during and after surgery, including impaired cough, atelectasis, acute bronchoconstriction, mucous plugging, hypoxemia, hypercapnia, and respiratory infection. The likelihood of complications is related to the severity of the patient's asthma and degree of symptom control before, during, and immediately after surgery. 4 The following are recommendations to help reduce the risk of complications during preoperative and postoperative elective nonemergent surgery.

Evaluation before surgery focuses on clinical symptoms, review of systems, medication adherence, medication use (especially oral steroids for >2 weeks in the past 6 months), clinical history, and spirometry (Box 2). 36 If oral corticosteroids were used for greater than 2 weeks in last 6 months, then the patient should receive stress dose intravenous hydrocortisone 100 mg every 8 hours during the surgical period followed by a lower dose within 24 hours after surgery. For select patients with history of high-dose ICS therapy (high-dose ICS is 500-2000 mg/d), stress doses of corticosteroids may also be indicated; clinically relevant adrenal suppression has been reported. 4, [37] [38] [39] If possible, an attempt to improve lung function preoperatively (FEV 1 or peak expiratory flow rate) to the patient's personal best or predicted values is recommended. A short course of oral corticosteroids can be considered in addition to daily controller drug therapy. Consider allergy or pulmonary consultation preoperatively if questions remain or the risk of pulmonary complications is considered very high.

Patients with COPD undergoing surgery are at an increased risk of postoperative pulmonary complications. Impaired ability or effectiveness of cough and acute bronchoconstriction can reduce lung function and cause sequelae from acute bronchoconstriction. Other complications include reintubation, prolonged intubation (>48 hours), aspiration pneumonia, and a prolonged intensive care unit (ICU) and hospital stay. The following recommendations apply to assessments before general surgery 12 :

The decision to proceed with surgical intervention is made between the consultant surgeon and anesthesiologist based on the patient's comorbidities, functional status, and necessity for surgery.

Composite assessment tools such as the American Society of Anesthesiologist Physical Status Classification System or American College of Surgeons National Surgical Quality Improve Program Surgical Risk Calculator should be used.

If able, medical management should be optimized before surgery, including a course of pulmonary rehabilitation, if applicable. Consider pulmonary consultation preoperatively for pulmonary optimization and if there is heightened concern for pulmonary complications.

Certain subpopulations of patients with COPD may benefit from NIV to assist spontaneous respirations. NIV provides a low-pressure ventilatory support system for patients who have an intact respiratory drive. The first step is to assess the stability of the patient with COPD for NIV including comorbid conditions such as obstructive sleep apnea (OSA), in which formal sleep testing is considered. A trial of continuous positive airway pressure or bilevel positive airway pressure therapy can also be considered.

The following patient populations can benefit from nocturnal NIV 40 :

Patients with daytime hypercapnia (arterial blood gases PaCO 2 >52 mm Hg). Oxygen desaturations during sleep (SpO 2 <88% for !5 minutes of !2 hours of nocturnal sleep oximetry despite use of supplemental oxygen !2 L/min via nasal cannula). Patients who have needed continuous NIV for acute exacerbations in the past.

Per the National Institute for Health and Care Excellence (NICE 2010) guidelines, 12 patients who have chronic hypercapnic respiratory failure requiring invasive ventilation or NIV during an exacerbation, or patients who are hypercapnic or acidotic on longterm oxygen therapy, should be referred to a pulmonologist. History of preoperative bronchospasm during/after previous surgery.

History of latex allergy.

Presence of gastroesophageal reflux, which can trigger bronchospasm.

Assess smoking status.

Absolute contraindications to NIV include uncooperative patients, respiratory arrest or unstable cardiopulmonary state, inability to protect the airway, and trauma or burns involving the face. Consider referral to a pulmonologist to discuss NIV, or whether an inpatient COPD team is available.

Hospitalized patients with asthma or COPD benefit from an integrated team of hospitalists and specialty clinicians. Once recognized, a severe asthma attack and severe AECOPD are potentially life-threatening events and can quickly lead to acute respiratory failure and death. Early institution of bronchodilator therapy; oxygen supplementation; systemic corticosteroids; mucus clearance; and, if indicated, antibiotics can reduce the risk of progressive respiratory failure. Once acute respiratory failure occurs, hospitalists must coordinate a rapid and coordinated critical care team response with ICU monitoring, use of NIV, and invasive mechanical ventilation where indicated.

Patients with asthma and with COPD should be encouraged to complete a selfmanagement plan on discharge to prevent recurrence and hospital readmission within 30 days. Education about the disease and implementing a written asthma action plan or COPD action plan should occur before discharge.

It is not necessary to achieve full resolution of asthma or COPD symptoms before discharge; however, it is critical that stability and safe functionality are established before discharge. With education and tailored evidence-based treatments coming from an experience interdisciplinary team led by hospitalists, patients are more likely to have shorter hospital lengths of stay, achieve regular outpatient follow-up, and ultimately reduce the rate of hospital readmission.

From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017

Chronic obstructive pulmonary disease (COPD), data and statistics

Expert panel report 3: guidelines for the diagnosis and management of asthma full report

Bronchodilator responsiveness in patients with COPD

Differentiating COPD from asthma in clinical practice

Differential assessment and management of asthma vs chronic obstructive pulmonary disease

Long-acting muscarinic antagonists (LAMA) added to combination long-acting beta-2 agonists and inhaled corticosteroids (LABA/ICS) versus LABA/ICS for adults with asthma

Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians

Acute exacerbations of COPD: avoiding danger and death

Chronic Obstructive pulmonary disease in over 16s: diagnosis and management

UC Davis Division of Pulmonary and Critical Care Medicine ROAD Center Program

Diagnosing asthma-COPD overlap syndrome

Diagnosis of Diseases of Chronic Airflow Limitations: Asthma COPD and Asthma -COPD Overlap Syndrome (ACOS)

Clinical characteristics of the asthma-COPD overlap syndrome-a systematic review

Asthma and chronic obstructive pulmonary disease overlap syndrome (ACOS): structured literature review and physician insights

The asthma-chronic obstructive pulmonary disease overlap syndrome: pharmacotherapeutic considerations

Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS): current literature review

Increased risk of exacerbation and hospitalization in subjects with an overlap phenotype: COPD-asthma

Prevalence and localization of pulmonary embolism in unexplained acute exacerbations of COPD

Prevalence of pulmonary embolism in acute exacerbations of COPD

Risk of pulmonary embolism and deep venous thrombosis in patients with asthma: a nationwide caseÀcontrol study from Sweden

Asthma increases pulmonary thromboembolism risk: a nationwide population cohort study

Asthma-chronic obstructive pulmonary disease overlap syndrome associated with risk of pulmonary embolism

Umeclidinium/vilanterol as step-up therapy from tiotropium in patients with moderate COPD: a randomized, parallel-group, 12-week study

Tiotropium bromide step-up therapy for adults with uncontrolled asthma

Tiotropium in asthma poorly controlled with standard combination therapy

Patient perspectives on fluticasone-vilanterol versus other corticosteroid combination products for the treatment of asthma

Effectiveness of fluticasone furoate-vilanterol for COPD in clinical practice

Evaluation of a therapeutic interchange from fluticasone/ salmeterol to mometasone/formoterol in patients with chronic obstructive pulmonary disease

Mometasone furoate/formoterol in the treatment of persistent asthma

Long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) versus LABA plus inhaled corticosteroid (ICS) for stable chronic obstructive pulmonary disease (COPD)

Efficacy of aclidinium bromide 400 mg twice daily compared with placebo and tiotropium in patients with moderate to severe COPD

Aclidinium bromide for stable chronic obstructive pulmonary disease

Control of asthma for reducing the risk of bronchospasm in asthmatics undergoing general anesthesia and/or intravascular administration of radiographic contrast media

Acute adrenal crisis in asthmatics treated with high-dose fluticasone propionate

Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom

The use of inhaled corticosteroids and the risk of adrenal insufficiency

Clinical indications for noninvasive positive pressure ventilation in chronic respiratory failure due to restrictive lung disease, COPD, and nocturnal hypoventilation-A consensus conference report